In the last ten to fifteen years there has been a profusion of proteins and cDNAs identified as being part of the myosin superfamily. Many are confirmed as true myosins by demonstrating their actin dependent ATPase activity and/or actin based motility. With an increasing number of examples and evidence of different myosins having a variety of cellular functions a number of groups have compared the protein sequences by producing alignments and phylogenetic trees.
Note that the alignment shown here is that published by Hodge and Cope in 2000. There have since been two further alignments completed that take account of newly-available data from recently-completed genomes.
1. Myosin domain evolution and the primary divergence of eukaryotes by Richards and Cavalier-Smith.
2. New insights into myosin evolution and classification by Foth et al.
3. Multiplying myosins. A useful commentary, published concurrently with the Foth et al tree, including a comparison of the two papers.
- We show here a new alignment
and tree produced by comparing the core motor domain sequences
of 143 myosins from the public databases. The
full alignment used to produce this tree is published on these
pages in plain text form, with secondary structural elements on
the chicken pectoralis muscle myosin II subfragment I structure
identified and shown above the
alignment. The alignment identifies a number of class and single
myosin specific inserts or substitutions in the core motor domain
in addition to forming the basis of the phylogenetic analysis.
Due to the large number of sequences involved it is difficult
to see the variability at each position at a glance - this requiring
the production of a more complex colour
alignment NB 1.5Mb of HTML! It is possible to save
the text from the plain alignment page for viewing in proprietary
We hope this will aid the correct positioning of important residues from any myosin on the framework of the crystal structure.
Phylogenetic Tree - An unrooted phylogenetic tree is presented, based on a similar tree published elsewhere (Hodge and Cope, 2000), derived from an alignment of 143 members of the myosin superfamily. The alignment compared the core motor domains (equivalent to amino acids 88 to 780 of chicken skeletal myosin II) of each myosin using distance matrix analysis performed with the Clustal-W package. The exceptions, shown with a dotted line, are SsVIIa, which is a partial sequence as reported in the databases and Hs MysPDZ. The latter is reported as a complete coding sequence but has a much truncated amino end starting some 52 residues into the core motor region (ie amino acid 140 of chicken skeletal myosin II). These shorter sequences have no significant effect on the branching order. (The implications of our original 82 myosin tree are discussed in more detail in Cope et al. 1996.) Each of the 17 classes shown is defined by a highly significant node, found in >90% of bootstrap trials, near the centre of the tree.
Optimally, when producing a phylogenetic tree from such an alignment, any positions in the alignment with gaps are excluded. Such a strategy would have excluded a large proportion of the data because of the large number of sequences. Positions with gaps were therefore included in the tree shown here. Comparison with a tree derived while excluding gaps showed some differences in branching order, but only within classes. The reliability of the tree structure was tested by several methods: 1) Bootstrapping (repeated redrawing of the tree structure, 1000 trials in this case) gave confidence levels for branching order (see below). 2) Alignments were re-ordered randomly and alphabetically by species or by taxa; these treatments gave trees with identical branching order within the classes. 3) Analysis of the alignment using protpars from the Phylip package (a maximum parsimony method) produced a tree with a similar branching order for most classes, the main exceptions being the single sequence classes.
Being unrooted (due to the lack of an "outgroup" or sequence from an accepted common ancestor), the relationships between classes as shown by the branching order at the centre of the tree is unreliable but evolutionary information can be derived within a class. Each class is defined by the first node represented in >90% of bootstrap trials starting from the centre of the tree. The inclusion of myosin sequence data recently added to the public databases has resulted in the clustering together at such a node of some of the more disparate examples based on their motor domains (Classes III, XII, XVI and the chitin synthase containing myosins). While this would normally be taken to define a class, the low sequence similarity (long branches), the lack of significance for this grouping obtained by maximum parsimony algorithms and general dissimilarity between complete molecules argue against such a classification. Analysis of the sequence identity of the two chitin synthase myosins (Pg csm1 and En csmA) shows they are orthologues, they also group together by distance matrix analysis with >90% confidence. This evidence allows us to define a new class (XVII) and the branches have been coloured accordingly.
The molecular cartoons serve to indicate possible molecular structure, especially the expected single or double headed nature of the myosins. Regarding the Myosin XIII cartoon, the '?' denotes one of the sequences (Acl myo1) having a surprisingly short tail which may reflect a sequence truncation.
A key for the nomenclature is given and is also included in the basic alignment page.
You may download a copy of the unrooted phylogenetic tree of myosins in Aldus Illustrator format (1Mb) but will need to email us for a password to unstuff this editable version. Alternatively click on the graphic (left) to get a full size jpeg version(NB 352Kb) - all we ask is that you use it as supplied, including the credits.
Alternatively you may wish to use the version published in JCS, also a jpeg.
It is immediately apparent that although the sequence region used for the analysis is confined to the motor domain in the myosin head, the classification of the myosins is almost exclusively consistent with that expected from examination of the tail regions, ie those thought to be responsible for interaction with the 'cargo' transported. There are also functional sub-classes eg the cardiac myosins are a distinguishable subset of the myosins II, indeed the late divergence of the skeletal and cardiac myosins in the myosins II illustrates the underlying trend for multiple myosins II to be required as multi-cellular organisms with specialised structures and tissues evolved.
Accessions - database entries for the myosins in the alignment and tree are available, as html links.
 Cope, M. Jamie
T. V., Whisstock, J., Rayment, I., and Kendrick-Jones, J. (1996)
Conservation within the myosin motor domain: Implications for
structure and function. Structure, 4, 969-987
 Hodge T and Cope M.J.T.V. (2000) A Myosin Family Tree. Journal of Cell Science 113, 3353-3354 (Tree in JPEG format)
Page initiated and produced by Jamie Cope and Tony Hodge.
Currently maintained by Brooke Morriswood.
If you use diagrams, trees, or sequence
alignments from the Myosin site, we ask that you cite either the
home page and authors, or the appropriate source publication in
Copyright 2000-2006 All rights reserved
Last updated 1st June 2006